Adequate animal glioma models are mandatory for the pursuit of preclinical research in neuro-oncology. Many implantation models have been described, but none perfectly emulate human malignant gliomas. This work reports our experience in standardizing, optimizing and characterizing the Fischer/F98 glioma model on the clinical, pathological, radiological and metabolic aspects.

F98 cells were implanted in 70 Fischer rats, varying the quantity of cells and volume of implantation solution, and using a micro-infusion pump to minimize implantation trauma, after adequate coordinates were established. Pathological analysis consisted in hematoxylin and eosin (H&E) staining and immunohistochemistry for GFAP, vimentin, albumin, TGF-b1, TGF-b2, CD3 and CD45. Twelve animals were used for MR imaging at 5, 10, 15 and 20 days. Corresponding MR images were compared with pathological slides. Two animals underwent 18F-FDG and 11C-acetate PET studies for metabolic characterization of the tumors.

Implantation with 1x104 cells produced a median survival of 26 days and a tumor take of 100%. Large infiltrative neoplasms with a necrotic core were seen on H&E. Numerous mitosis, peritumoral infiltrative behavior, and neovascular proliferation were also obvious. GFAP and vimentin staining was positive inside the tumor cells. Albumin staining was observed in the extracellular space around the tumors. CD3 staining was negligible. The MR images correlated the pathologic findings. 18F-FDG uptake was strong in the tumors.

The standardized model described in this study behaves in a predictable and reproducible fashion, and could be considered for future pre-clinical studies. It adequately mimics the behavior of human malignant astrocytomas.

To determine: 1. the degrees of consensus and disagreement among Canadian critical care clinicians regarding the appropriateness (benefit exceeding risk) of common therapeutic manoeuvres in patients with severe closed head injury (CHI), and 2. the frequency with which clinicians employed these manoeuvres.

The study design was a systematic scenario-based survey of all neurosurgeons and critical care physicians treating patients with severe CHI in Canada.

In the scenario of acute epidural hematoma with mass effect, respondents agreed very strongly that surgery was appropriate. Clinicians reported mannitol and hypertonic saline as appropriate. Beyond these two interventions, agreement was less strong, and the use of the extraventricular drain (EVD), phenytoin, cooling, hyperventilation, nimodipine, and jugular venous oximetry (JVO) were of uncertain appropriateness. Steroids were considered inappropriate. In a scenario of diffuse axonal injury (DAI), clinicians agreed strongly that fever reduction, early enteral feeding, intensive glucose control, and cerebral perfusion pressure (CPP)-directed management were appropriate. The use of mannitol, hypertonic saline, EVD, JVO, narcotics and propofol were also appropriate. Neuromuscular blockade, surgery, and hyperventilation were of uncertain appropriateness. The appropriateness ratings of the interventions considered in the scenario of an intracranial contusion mirrored the DAI scenario. In general, correlations between the reported appropriateness and frequency of use of each intervention were very high. An exception noted was the use of the JVO. The correlation between CPP-guided therapy and the use of the EVD was weak.

This survey has described current practice with regard to treatment of patients with severe CHI. Areas of variation in perceived appropriateness were identified that may benefit from further evaluation. Suggested priorities for evaluation include the use of osmotic diuretics, anticonvulsants, and intracranial manometry.

The central and peripheral nervous systems are often affected in intensive care unit (ICU) patients, especially those with prolonged assisted ventilation and sepsis or systemic inflammatory response syndrome (SIRS). The autonomic nervous system, however, has been under-investigated in such patients. We evaluated autonomic nervous system (ANS) function in 29 ICU patients with various neurological disorders.

Testing involved cardiac R-R variation (CRRV) as an index of parasympathetic function and the sympathetic skin response (SSR) for sympathetic assessment.

Only those 8 patients with sepsis-related neuropathy or encephalopathy had abnormal CRRV, while the SSR was absent in all but 2 patients.

Our preliminary study revealed a high incidence of autonomic dysfunction in ICU patients with various neurological disorders.

Posterior reversible encephalopathy syndrome (PRES) occurs most commonly in the setting of known hypertension or use of immunosuppressive agents.

We report four previously-well children who presented acutely with altered mentation, seizures and visual disturbances and were diagnosed with PRES.

Only one child had a history of gross hematuria prior to the seizure. All four were discovered to be hypertensive only after onset of their neurological symptoms, and were subsequently diagnosed with glomerulonephritis. All four had rapid resolution of neurological symptoms with adequate treatment of hypertension.

Blood pressure must be measured promptly in all children presenting with these symptoms. If elevated, the diagnosis of PRES should be strongly considered and a workup for renal disease pursued.

Metastasis to the pituitary gland is unusual, and occurs most often in patients with carcinomas of the breast or lung. Despite its propensity for spread to the brain, metastatic melanoma has rarely been described within the sella.

We report two cases of malignant melanoma pathologically confirmed within the pituitary, both metastatic from a primary site on the chest wall. In each patient, transsphenoidal resection of the tumor was incomplete and each received local radiotherapy after surgery.

One patient recurred quickly and developed brain metastasis as well. He died four months after resection of the pituitary metastasis, but the second patient survived six months without recurrence. As intrasellar metastasis portends widespread systemic disease and may be synchronous with parenchymal brain metastasis, survival in such patients is limited regardless of adjunctive therapy.

Such cases are likely to arise more commonly in future due to the increasing incidence of melanoma. Identifying them by imaging alone is difficult due to inconsistent signal characteristics on MRI (as shown by these cases) and the confusion introduced by any associated intratumoral hemorrhage.

Kennedy's disease (KD) is an X-linked recessive polyglutamine disease. Traditionally, it is a lower motor neuron syndrome with additional features such as gynecomastia and tremor. Sensory symptoms are minimal if ever present. We used multimodal evoked potential (EPs) tests to study the distribution of the involvement of the disease.

Visual, brainstem auditory, somatosensory and motor EPs were studied in six KD patients. All of them had typical presentations and had been proved genetically.

Abnormal findings were noted as follows: prolonged peak latencies of visual EPs, increased hearing threshold level, inconsistent brainstem auditory EPs, decreased amplitudes of cortical potentials of somatosensory EPs, and increased motor threshold to transcranial magnetic stimulation.

Our multimodal EP studies showed that KD involved multiple levels of the nervous system. It implies the widespread effects of the mutant androgen receptors.

An old founder mutation (G2019S) was found with high frequency in the North African Arabs (30%) and Ashkenazi Jews (18%).

Demonstrate if mutations in the LRRK2 gene are a significant cause of Parkinson's disease (PD) in the French-Canadian founder population.

Cases were recruited through a designated movement disorder clinic in Quebec City. Every index case had to meet the Ward and Gibb criteria for PD. Controls consisted of a non-disease group of similar age and ethnicity as the cases. Exons 31 and 41 of LRRK2 were amplified by PCR with intronic primers in all 125 PD cases and directly sequenced on an ABI 3700 sequencer. Six single nucleotide polymorphism were typed in 125 PD cases and 95 normal controls. Associations between unrelated cases and matched controls were analyzed. Single marker analysis and haplotype association tests were performed.

Sequencing analysis did not reveal any reported or novel mutations in exons 31 and 41 of LRRK2. The G2019S mutation as well as mutations affecting amino acid 1441 were absent in the 125 patients. The case-control association study performed to detect the presence of a common variant in LRRK2 did not provide any positive signal. Single-marker and haplotype analyses systematically gave non-significant P values.

We performed a case-control association study in 125 French-Canadian (FC) patients with PD and 95 FC controls and found that common variants in LRRK2 are unlikely to be a significant cause of late-onset PD in this founder population.

Mutations in the leucine-rich repeat kinase 2 gene (LRRK2) have become the most common known cause for developing Parkinson's disease. The frequency of mutations described in the literature varies widely depending on the population studied with most reports focusing only on screening for the most common G2019S mutation in exon 41.

In this study seven exons (19, 24, 25, 31, 35, 38, and 41) in LRRK2 where mutations have been reported were screened in 230 unselected Parkinson's disease patients using denaturing high-performance liquid chromatography.

The sequencing of samples with heteroduplex profiles revealed five novel and two known intronic sequence variants. In our cohort, we were unable to detect any of the known mutations in these exons or identify novel mutations within the LRRK2 gene.

Therefore, despite the availability of diagnostic LRRK2 genetic testing it is unlikely to yield a positive result in this population.

Very long term survival after diagnosis of malignant glioma has been described in individual case reports. Survival of more than 10 years is extremely rare, especially when identified in 3 out of 71 patients assigned to one arm of a randomized controlled trial.

Three patients survived 11, 16, and 18 years following the diagnosis of glioblastoma and treatment with surgery, conventional fractionated radiation, and high-activity iodine-125 boost brachytherapy as part of a randomized controlled trial.

Despite this apparent cause and effect relationship, statistical analysis shows no relationship between these cures and treatment with brachytherapy. Cure of glioblastoma remains rare.

Our objective is to examine how persons diagnosed with Multiple Sclerosis (MS) and Parkinson's disease (PD) change residence following disease onset. We hypothesize that persons choose to change residence (locally or regionally) in different ways depending on whether or not they have been diagnosed with MS/PD. We also estimate the effects of residence change on measures of disease prevalence made at several different levels of geography.

Using fee-for service and hospitalization data, we identify cases of MS and PD between 1994 and 2004. Both of these case groups are matched to controls based on age, sex, socioeconomic status and municipality of residence. We tabulate and compare the changes of residence among persons in the case and control groups. We also use these data to estimate the effects that changes in residence have on disease prevalence at three different levels of geography.

Both MS and PD patients were more likely to change residence following disease onset compared to groups of matched controls (p<=0.001). Most changes of residence occur within the same municipality. The total magnitude of these changes is small, however, and is unlikely to affect estimates of disease prevalence; over our study period, the largest change in geographical prevalence estimates due to individual changes in residence was about 1%.

Persons diagnosed with MS and PD both have mobility characteristics that differ from those of their respective control groups, and in general, are more likely to move to or between Edmonton and Calgary, and less likely to move out of province. However, the balance of mobility characteristics of persons with PD and MS appear unlikely to greatly affect the patterns observed on maps of disease prevalence.

This critical review provides a summary of the clinical presentation, neuroimaging, treatment and prognosis in pediatric ophthalmoplegic migraine (OM). The features of OM are not in keeping with its classification as a migraine-variant.

We review 3 new and 37 reported pediatric OM cases.

Headache was an inconsistent feature, with 25% patients showing no evidence of pain at the initial OM episode.

1) prolonged time for symptom resolution to occur (median time 3 weeks); 2) tendency for recurrent episodes to have more severe and persistent nerve involvement; 3) evidence of permanent neurological sequelae with recurrent episodes (30% of patients); 4) rapid improvement and shortened duration with corticosteroid therapy and; 5) transient, reversible MRI contrast enhancement of the affected cranial nerve (86% of patients). These features would not be expected in primary migraine headache.

A detailed understanding of the natural history of OM is essential for the clinical. This review provides support that OM may result from cranial nerve inflammation with headache a secondary and later feature of this condition.

Oxidative stress largely contributes to early brain injury after subarachnoid hemorrhage (SAH). One of the major sources of reactive oxygen species is NADPH oxidase, upregulated after SAH. We hypothesized that NADPH oxidase-induced oxidative stress plays a major causative role in early brain injury after SAH.

Using gp91phox knockout (ko) and wild-type (wt) mice, we studied early brain injury in the endovascular perforation model of SAH. Mortality rate, cerebral edema, oxidative stress, and superoxide production were measured at 24 h after SAH. Neurological evaluation was done at 23 h after SAH surgery.

Genotyping confirmed the existence of a nonfunctional gp91phox gene in the ko mice. CBF measurements did not show differences in SAH-induced acute ischemia between ko and wt mice. SAH caused a significant increase of water content in the ipsilateral hemisphere as well as an increase of Malondialdehyde (MDA) levels and superoxide production. There were no significant differences in post-SAH mortality rate, brain water content and the intensity of the oxidative stress between knockout and wild type groups of mice.

Our results suggest that gp91phox is not critically important to the early brain injury after SAH. An adaptive compensatory mechanism for free radical production in knockout mice is discussed.